Two-photon microscopy is revolutionizing many aspects of modern microscopy and having a dramatic impact upon biomedical research in general. The major advantages provided by two-photon instruments are the ability to image deep within tissue samples and the greatly enhanced abilities for live-cell work. Taken together, these technical capabilities open up an enormous array of novel strategies for investigators.Funds are requested for the purchase of a 2- photon microscope, composed of a Zeiss (LSM 510) laser scanning confocal microscope and a Chameleon XR Ti:Sapphire laser acquired from Coherent, providing femtosecond pulses compatible with live-tissue imaging. The instrument will be integrated into the UCSB Shared Microscopy Facility. This communal core facility, operated jointly by our Neuroscience Research Institute (an interdisciplinary Organized Research Unit of the University of California) and our Department of Molecular, Cellular and Developmental Biology has been providing shared microscopy instrumentation and technical support to UCSB investigators for 17 years. The full-time Director of the Facility, Dr. Brian Matsumoto, is an acknowledged expert in multiple aspects of cutting-edge microscopy. Presently, the major instrumentation in the Facility includes an Olympus Fluoview Confocal Laser Scanning Microscope, a JEOL transmission electron microscope, and four state-of-the-art Olympus fluorescence microscopes with digital cameras. The confocal and electron microscopes were both acquired via the Shared Instrumentation Program, and both have been used extensively and maintained meticulously. Various NIH-funded investigators at UCSB will benefit from the expanded repertoire of applications provided by this instrument, including the ability to image deep within tissue samples and the in-vitro analysis of living cells or tissues across time in the absence of the phototoxicity typically associated with single-photon approaches. Acquisition of this 2-photon microscope will therefore enhance the diverse efforts of a number of investigators at UCSB in pursuit of their NIH-funded research objectives. [unreadable] [unreadable] [unreadable]